To keep the plasma level of a drug constant for long hours has many merits not only to enhance preventing or curing diseases,but also to reduce administration times of the drug and to improve the compliance of the patient. Therefore, many kinds of controlled release preparations which control drug release rate from the preparation have been developed and used extensively.
For example, in Japanese Patent Publication No. 11699/1995 a tablet in which a core portion containing a drug (nifedipine) is rapidly released and is coated compressively with a coating material consisting of a hydrophilic gelforming polymer and the drug is described. On administration of this tablet once a day the suitable continuation is attained, but it is not satisfied enough and, in addition to that, there is such a problem that it needs two step-compressing procedures to prepare such a tablet. These are troublesome.
Besides, different from the above preparation, membrane-coated granules and membrane-coated tablets, which are prepared by coating the core portion or an uncoated core-tablet containing a drug with a water-insoluble polymer and a water-soluble polymer, and matrix tablets which are prepared by compressing a drug with a water-insoluble polymer or wax, etc. and so on are evaluated. In such preparations, because the drug release rate is reduced with the lapse of time on administration in vivo, the plasma level of the drug is reduced from time to time. There is such a problem that it is difficult to keep the plasma level of the drug for long hours.
Recently the relationship between circadianrhythm and disease has been given attention to and it becomes important to consider the circadianrhythm in the medical treatment.
From the facts mentioned above, the improvement of controlled release preparations has in various respects have been studied.